[The study of apoptosis factors released from laser injured cartilage inducing apoptosis of chondrocyte]

OBJECTIVE: To explore the role of pro-apoptotic signals following tissue injury and how these may promote a progression of further cell death. METHODS: Laser treated porcine articular cartilage disks were maintained in culture media. The collected media at various time periods (3, 6, 9, 12, 24 and 48 h), was called treated conditioned media (TCM). Non-laser treated cartilage disks were used to create control conditioned media (CCM). Each disk was subsequently maintained for 28 days and used in confocal microscopic assessment to document the progression of the damaged area. Isolated porcine chondrocytes were cultured in monolayer, and were exposed to TCM, CCM or normal culture medium (NM). As a positive inducer of apoptosis, the monolayer cells were exposed to UV radiation for 10 min and cultured in NM. Following 24 h exposure, the cells were harvested and stained with the appropriate combination of fluorescent dyes and processed via flow cytometry. RESULTS: All cultured cells exposed to TCM displayed a caspase-3 positive subpopulation, a loss of CMXRos, and with a reduced or lost NO signal. CCM exposure signals were comparable to the NM treatments with all having retained CMXRos, NO and without evidence of caspase-3 activity. UV treatment also induced a reduction in NO, but both CMXRos and caspase-3 positive, representing an earlier stage of apoptosis and suggesting that the mode of cell death via UV and TCM exposure are via different processes. The investigation of a dose (100%, 50%, 25% and 12.5%) and time (0.5, 1, 3, 9, 12 h) response to TCM exhibited that all treatments observed an increase in caspase-3 positive cells and a reduction in NO and CMXRos. CONCLUSION: The usefulness of FCM can be used in the study of cell viability and apoptosis. Such a system may be useful in the study of mechanisms of disease such as osteoarthritis, thus may be of practical use for the pharmaceutical industry for screening associated drugs.

CT dose and image quality in the last three scanner generations.

AIM To compare the computed tomography (CT) dose and image quality with the filtered back projection against the iterative reconstruction and CT with a minimal electronic noise detector. METHODS A lung phantom (Chest Phantom N1 by Kyoto Kagaku) was scanned with 3 different CT scanners: the Somatom Sensation, the Definition Flash and the Definition Edge (all from Siemens, Erlangen, Germany). The scan parameters were identical to the Siemens presetting for THORAX ROUTINE (scan length 35 cm and FOV 33 cm). Nine different exposition levels were examined (reference mAs/peek voltage): 100/120, 100/100, 100/80, 50/120, 50/100, 50/80, 25/120, 25/100 and 25 mAs/80 kVp. Images from the SOMATOM Sensation were reconstructed using classic filtered back projection. Iterative reconstruction (SAFIRE, level 3) was performed for the two other scanners. A Stellar detector was used with the Somatom Definition Edge. The CT doses were represented by the dose length products (DLPs) (mGycm) provided by the scanners. Signal, contrast, noise and subjective image quality were recorded by two different radiologists with 10 and 3 years of experience in chest CT radiology. To determine the average dose reduction between two scanners, the integral of the dose difference was calculated from the lowest to the highest noise level. RESULTS When using iterative reconstruction (IR) instead of filtered back projection (FBP), the average dose reduction was 30%, 52% and 80% for bone, soft tissue and air, respectively, for the same image quality (P < 0.0001). The recently introduced Stellar detector (Sd) lowered the radiation dose by an additional 27%, 54% and 70% for bone, soft tissue and air, respectively (P < 0.0001). The benefit of dose reduction was larger at lower dose levels. With the same radiation dose, an average of 34% (22%-37%) and 25% (13%-46%) more contrast to noise was achieved by changing from FBP to IR and from IR to Sd, respectively. For the same contrast to noise level, an average of 59% (46%-71%) and 51% (38%-68%) dose reduction was produced for IR and Sd, respectively. For the same subjective image quality, the dose could be reduced by 25% (2%-42%) and 44% (33%-54%) using IR and Sd, respectively. CONCLUSION This study showed an average dose reduction between 27% and 70% for the new Stellar detector, which is equivalent to using IR instead of FBP.

Lung cancer screening with CT: evaluation of radiologists and different computer assisted detection software (CAD) as first and second readers for lung nodule detection at different dose levels

OBJECTIVES To find the best pairing of first and second reader at highest sensitivity for detecting lung nodules with CT at various dose levels. MATERIALS AND METHODS An anthropomorphic lung phantom and artificial lung nodules were used to simulate screening CT-examination at standard dose (100 mAs, 120 kVp) and 8 different low dose levels, using 120, 100 and 80 kVp combined with 100, 50 and 25 mAs. At each dose level 40 phantoms were randomly filled with 75 solid and 25 ground glass nodules (5-12 mm). Two radiologists and 3 different computer aided detection softwares (CAD) were paired to find the highest sensitivity. RESULTS Sensitivities at standard dose were 92%, 90%, 84%, 79% and 73% for reader 1, 2, CAD1, CAD2, CAD3, respectively. Combined sensitivity for human readers 1 and 2 improved to 97%, (p1=0.063, p2=0.016). Highest sensitivities--between 97% and 99.0%--were achieved by combining any radiologist with any CAD at any dose level. Combining any two CADs, sensitivities between 85% and 88% were significantly lower than for radiologists combined with CAD (p<0.03). CONCLUSIONS Combination of a human observer with any of the tested CAD systems provide optimal sensitivity for lung nodule detection even at reduced dose at 25 mAs/80 kVp.

Optimal dose levels in screening chest CT for unimpaired detection and volumetry of lung nodules, with and without computer assisted detection at minimal patient radiation

OBJECTIVES The aim of this phantom study was to minimize the radiation dose by finding the best combination of low tube current and low voltage that would result in accurate volume measurements when compared to standard CT imaging without significantly decreasing the sensitivity of detecting lung nodules both with and without the assistance of CAD. METHODS An anthropomorphic chest phantom containing artificial solid and ground glass nodules (GGNs, 5-12 mm) was examined with a 64-row multi-detector CT scanner with three tube currents of 100, 50 and 25 mAs in combination with three tube voltages of 120, 100 and 80 kVp. This resulted in eight different protocols that were then compared to standard CT sensitivity (100 mAs/120 kVp). For each protocol, at least 127 different nodules were scanned in 21-25 phantoms. The nodules were analyzed in two separate sessions by three independent, blinded radiologists and computer-aided detection (CAD) software. RESULTS The mean sensitivity of the radiologists for identifying solid lung nodules on a standard CT was 89.7% ± 4.9%. The sensitivity was not significantly impaired when the tube and current voltage were lowered at the same time, except at the lowest exposure level of 25 mAs/80 kVp [80.6% ± 4.3% (p = 0.031)]. Compared to the standard CT, the sensitivity for detecting GGNs was significantly lower at all dose levels when the voltage was 80 kVp; this result was independent of the tube current. The CAD significantly increased the radiologists' sensitivity for detecting solid nodules at all dose levels (5-11%). No significant volume measurement errors (VMEs) were documented for the radiologists or the CAD software at any dose level. CONCLUSIONS Our results suggest a CT protocol with 25 mAs and 100 kVp is optimal for detecting solid and ground glass nodules in lung cancer screening. The use of CAD software is highly recommended at all dose levels.

Impact of perioperative chemotherapy on survival in patients with advanced primary urethral cancer: results of the international collaboration on primary urethral carcinoma.

BACKGROUND To investigate the impact of perioperative chemo(radio)therapy in advanced primary urethral carcinoma (PUC). PATIENTS AND METHODS A series of 124 patients (86 men, 38 women) were diagnosed with and underwent surgery for PUC in 10 referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank testing was used to investigate the impact of perioperative chemo(radio)therapy on overall survival (OS). The median follow-up was 21 months (mean: 32 months; interquartile range: 5-48). RESULTS Neoadjuvant chemotherapy (NAC), neoadjuvant chemoradiotherapy (N-CRT) plus adjuvant chemotherapy (ACH), and ACH was delivered in 12 (31%), 6 (15%) and 21 (54%) of these patients, respectively. Receipt of NAC/N-CRT was associated with clinically node-positive disease (cN+; P = 0.033) and lower utilization of cystectomy at surgery (P = 0.015). The objective response rate to NAC and N-CRT was 25% and 33%, respectively. The 3-year OS for patients with objective response to neoadjuvant treatment (complete/partial response) was 100% and 58.3% for those with stable or progressive disease (P = 0.30). Of the 26 patients staged ≥cT3 and/or cN+ disease, 16 (62%) received perioperative chemo(radio)therapy and 10 upfront surgery without perioperative chemotherapy (38%). The 3-year OS for this locally advanced subset of patients (≥cT3 and/or cN+) who received NAC (N = 5), N-CRT (N = 3), surgery-only (N = 10) and surgery plus ACH (N = 8) was 100%, 100%, 50% and 20%, respectively (P = 0.016). Among these 26 patients, receipt of neoadjuvant treatment was significantly associated with improved 3-year relapse-free survival (RFS) (P = 0.022) and OS (P = 0.022). Proximal tumor location correlated with inferior 3-year RFS and OS (P = 0.056/0.005). CONCLUSION In this series, patients who received NAC/N-CRT for cT3 and/or cN+ PUC appeared to demonstrate improved survival compared with those who underwent upfront surgery with or without ACH.

[Fixed-combination of losartan/hydrochlorothiazide 100 mg/25 mg. Tolerability and efficacy on blood pressure measured in the practice and for 24 hours]

BACKGROUND: A high proportion of patients with essential hypertension need a combination therapy to reach the therapeutic goal. In the present study, the tolerability and efficacy of a fixed, once daily combination of the AT1 blocker Losartan (100 mg) and the diuretic hydrochlorothiazide (HCTZ) (25 mg) for patients in the real-life situation was investigated. Special consideration was given to the results of ambulatory 24-hourblood pressure (ABP) measurements. METHODS: The open label, prospective non-interventional surveillance study took place from October 2005 to June 2006. A total of 1139 patients over 18 years in age were included whose blood pressures could not be adequately treated with HCTZ alone and for whom an individual dose titration for Losartan and HCTZ had already been performed. RESULTS: The average age (+/- standard deviation) of the patients was 61.2 +/- 11.6 years; 55.8% were men. Comorbidities were common. Specifically, left ventricular hypertrophy was present in 3.1% of the patients, coronary heart disease in 30.1%, chronic heart failure in 11.8% and status post myocardial infarction in 10.5%, respectively. In addition to the Losartan/HCTZ treatment, 61.0% of the patients received a second antihypertensive medicine. After an average treatment duration of 50.4 +/- 17.2 days, the base line systolic blood pressure of 160.8 +/- 16.3 mmHg decreased by 24.0 +/- 17.0 mmHg (-14.4%) and the diastolic blood pressure of 94.4 +/- 9.9 mmHg decreased by 11.8 +/- 10.2 mmHg (-11.8%). For the ABP measurements, the overall average systolic and diastolic blood pressures fell by 16.9 +/- 14.2 mmHg and 8.8 +/-10.3 mmHg, the day average by 17.3 +/- 14.8 mmHg and 9.0 +/- 10.2 mmHg and the night average by 15.1 +/- 17.6 mmHg and 7.8 +/- 11.7 mmHg, respectively. In twelve of the 1139 patients (1.1%), a total of 15 adverse events occurred. A causal connection with the medication was suspected in only in one case (one patient with three). CONCLUSION: The combination of Losartan/HCTZ 100/25 mg, as the exclusive therapy or in addition to other antihypertensive medicines, was for patients, many of whom who had comorbidities, in the real-life situation well tolerated and effective. The efficacy was demonstrated also during the night through ABP.

Is body weight the most appropriate criterion to select patients eligible for low-dose pulmonary CT angiography? Analysis of objective and subjective image quality at 80 kVp in 100 patients

The objective of this retrospective study was to assess image quality with pulmonary CT angiography (CTA) using 80 kVp and to find anthropomorphic parameters other than body weight (BW) to serve as selection criteria for low-dose CTA. Attenuation in the pulmonary arteries, anteroposterior and lateral diameters, cross-sectional area and soft-tissue thickness of the chest were measured in 100 consecutive patients weighing less than 100 kg with 80 kVp pulmonary CTA. Body surface area (BSA) and contrast-to-noise ratios (CNR) were calculated. Three radiologists analyzed arterial enhancement, noise, and image quality. Image parameters between patients grouped by BW (group 1: 0-50 kg; groups 2-6: 51-100 kg, decadally increasing) were compared. CNR was higher in patients weighing less than 60 kg than in the BW groups 71-99 kg (P between 0.025 and <0.001). Subjective ranking of enhancement (P = 0.165-0.605), noise (P = 0.063), and image quality (P = 0.079) did not differ significantly across all patient groups. CNR correlated moderately strongly with weight (R = -0.585), BSA (R = -0.582), cross-sectional area (R = -0.544), and anteroposterior diameter of the chest (R = -0.457; P < 0.001 all parameters). We conclude that 80 kVp pulmonary CTA permits diagnostic image quality in patients weighing up to 100 kg. Body weight is a suitable criterion to select patients for low-dose pulmonary CTA.

Abnormalities of very low density lipoprotein apolipoprotein B-100 metabolism contribute to the dyslipidaemia of adult growth hormone deficiency

Increased cardiovascular mortality in adult growth hormone deficiency (GHD) may be, in part, explained by the dyslipidaemia associated with this condition. It is possible that abnormalities of very low density lipoprotein apolipoprotein B-100 (VLDL apoB) metabolism contribute to this dyslipidaemia. To test this hypothesis, we measured VLDL apoB kinetics in adult GH deficient patients (4 females, 3 males; age 50.1 +/- 4.7 yr (mean +/- SEM); BMI 28.2 +/- 1.1 kg/m2; total cholesterol (TC) 6.6 +/- 0.3 mmol/l; triglyceride (TG) 2.8 +/- 0.6 mmol/l; HDL cholesterol 1.1 +/- 0.1 mmol/l) and in control subjects (4 females, 3 male; age 47.0 +/- 4.7 yr; BMI 27.0 +/- 2.6 kg/m2; TC 5.0 +/- 0.4 mmol/l; TG 0.9 +/- 0.2 mmol/l; HDL cholesterol 1.4 +/- 0.1 mmol/l). [1-(13)C] leucine was administered by a primed (1 mg/kg), constant intravenous infusion (1 mg/kg/hr) and VLDL apoB enrichment with 13C leucine was determined using gas-chromatography mass-spectrometry. The GHD patients had a significantly higher hepatic secretion rate of VLDL apoB (15.5 +/- 1.8 mg/kg/day vs 9.4 +/- 0.6 mg/kg/day p = 0.007) and reduced catabolism ofVLDL apoB (metabolic clearance rate; 12.3 +/- 1.7 ml/min vs 24.3 +/- 4.8 ml/min p < 0.05) compared with control subjects. These findings suggest that GH is integrally involved in the regulation of VLDL apoB metabolism.

Pulsed versus continuous wave CO2 laser excisions of 100 oral fibrous hyperplasias: a randomized controlled clinical and histopathological study

BACKGROUND In experimental animal studies, pulsing the CO2 laser beam has been shown to reduce the thermal damage zone of excised oral mucosal tissue. However, there is still controversy over whether this is borne out under clinical conditions. OBJECTIVE To compare the outcome following excisional biopsies of fibrous hyperplasias using a pulsed (cf) versus a continuous wave (cw) CO2 laser mode regarding the thermal damage zone, duration of surgeries, intra- and postoperative complications, postoperative pain sensation, scarring and/or relapse during the initial 6 months. MATERIALS AND METHODS One hundred Swiss-resident patients with a fibrous hyperplasia in their buccal mucosa were randomly assigned to the cw mode (5 W) or the cf mode (140 Hz, 400 microseconds, 33 mJ, 4.62 W) group. All excisions were performed by one single oral surgeon. Postoperative pain (2 weeks) was recorded by visual analogue scale (VAS; ranging from 0 to 100). Intake of analgesics and postoperative complications were recorded in a standardized study form. The maximum width of the collateral thermal damage zone was measured (µm) in excision specimens by one pathologist. Intraoral photographs at 6-month follow-up examinations were evaluated regarding scarring (yes/no). RESULTS Median duration of the excision was 65 seconds in the cw and 81 seconds in the cf group (P = 0.13). Intraoperative bleeding occurred in 16.3% of the patients in the cw and 17.7% of the cf group. The median value of the thermal damage zone was 161(±228) μm in the cw and 152(± 105) μm in the cf group (P = 0.68). The reported postoperative complications included swelling in 19% and minor bleeding in 6% without significant differences between the two laser modes. When comparing each day separately or the combined mean VAS scores of both groups between Days 1-3, 1-7, and 1-15, there were no significant differences. However, more patients of the cw group (25%) took analgesics than patients of the cf group (9.8%) resulting in a borderline significance (P = 0.04). Scarring at the excision site was found in 50.6% of 77 patients after 6 months, and more scars were identified in cases treated with the cf mode (P = 0.03). CONCLUSIONS Excision of fibrous hyperplasias performed with a CO2 laser demonstrated a good clinical outcome and long-term predictability with a low risk of recurrence regardless of the laser mode (cf or cw) used. Scarring after 6 months was only seen in 50.6% of the cases and was slightly more frequent in the cf mode group. Based on the findings of the present study, a safety border of 1 mm appears sufficient for both laser modes especially when performing a biopsy of a suspicious soft tissue lesion to ensure a proper histopathological examination.